Poly-4-hydroxybutyrate (P4HB, TephaFLEX® biomaterial) is a strong, pliable thermoplastic polyester that, despite its biosynthetic route, has a relatively simple structure. Upon implantation, P4HB hydrolyzes to its monomer, and the monomer is metabolized via the Krebs cycle to carbon dioxide and water. The polymer belongs to a larger class of materials called polyhydroxyalkanoates (PHAs) that are produced by numerous microorganisms (Steinbüchel, et al., FEMS Microbial. Lett. 128:219-228 (1995)). They are of commercial interest because of their thermoplastic properties, biodegradability and relative ease of production.
The PHA polymers have a diverse range of mechanical properties. For example, P4HB has entirely different physical and chemical properties from poly-3-hydroxybutyrate (P3HB, also commonly referred to as PHB) even though it belongs to the same polymer family. For example, P4HB has a melt temperature of 61° C. compared to a melt temperature of 180° C. for P3HB, and the elongation to break of P4HB is about 1,000% compared to just a few percent for P3HB. P4HB and P3HB also do not share the same molecular structure, and therefore have different crystallization rates, and whereas P4HB is a strong pliable and tough thermoplastic P3HB is a relatively brittle material. In fact, in terms of mechanical properties, P4HB has properties more similar to low density polypropylene than to the properties of P3HB.
Medical devices and applications of P4HB are disclosed by WO 00/56376 to Williams et al. Several patents including U.S. Pat. Nos. 6,514,515, 6,555,123, 6,585,994, 7,025,980, and WO 2005/020825 describe the use of PHAs in tissue repair and engineering.
In the practice of surgery there currently exists a need for resorbable structures with high tensile strength and high modulus. These structures must have prolonged strength retention, and be able to breakdown in vivo without releasing inflammatory products. U.S. Pat. Nos. 8,034,270, 8,016,883, 8,287,909, WO 2011/119742 and WO 2011/159784 disclose fibers, non-wovens, and textiles made by melt extrusion of P4HB. WO 2008/070428 discloses films made by solvent and melt extrusion of P4HB.
In contrast to melt extrusion processing (where polymer powder or pellets are melt extruded and oriented by stretching of the extrudate to form crystalline structures), pultrusion is a process whereby un-oriented polymeric rods are pulled through a series of profile dies to provide a reduced profile with high modulus and tensile strength. Thus, although P4HB has been extruded to produce, for example, films and fibers, as well as injection molding of P4HB, there is no disclosure of P4HB products made by pultrusion.
It is therefore an object of the present invention to provide compositions including P4HB and copolymers thereof, which can be processed by pultrusion to impart higher strength and stiffness without conventional stretching and without causing damage to the surface of the profile.
It is also an object of the invention to provide continuous processes for pultrusion of compositions including poly-4-hydroxybutyrate and copolymers thereof, which can be incorporated into, processed or formed into medical products with excellent physical and mechanical properties for medical applications.
It is another object of the present invention to provide a method of processing compositions of P4HB homopolymers, or copolymers thereof by pultrusion.
It is still another object of the present invention to provide profiles made from compositions of P4HB and copolymers thereof by pultrusion.
It is still further an object of the present invention to provide profiles of compositions of P4HB and copolymers thereof with enhanced mechanical properties and controlled degradation rates that can be used in medical applications.